RESUMEN
Progression-free survival after R-High CHOP/CHASER/LEED with auto-PBSCT in untreated mantle cell lymphoma in JCOG0406 study. A continuous pattern of relapse was observed.
Asunto(s)
Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/diagnóstico por imagen , Linfoma de Células del Manto/tratamiento farmacológico , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia , Rituximab/uso terapéutico , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Prednisona/uso terapéuticoRESUMEN
We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti-HBV prophylactic therapy: no nucleos(t)ide analogue (non-NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non-NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non-NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Casos y Controles , Ciclofosfamida/administración & dosificación , ADN Viral/sangre , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Hepatitis B/sangre , Hepatitis B/epidemiología , Virus de la Hepatitis B/genética , Humanos , Incidencia , Quimioterapia de Inducción/métodos , Japón/epidemiología , Pruebas de Función Hepática , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/virología , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Retrospectivos , Rituximab/administración & dosificación , Análisis de Supervivencia , Vincristina/administración & dosificación , Activación ViralRESUMEN
A 67-year-old male was referred to our hospital because of anemia, thrombocytopenia, and massive ascites. A diagnosis of systemic mastocytosis was made based on the observation of many mast cells in his bone marrow, elevated serum tryptase levels, and the presence of c-kit point mutation Asp816Val. Dasatinib and cladribine were ineffective, and a large volume of ascites was removed approximately every 3 days. Then, following an asthma attack, the patient was treated with pranlukast, a leukotriene receptor antagonist (LTRA). After LTRA treatment initiation, the frequency of ascites drainage decreased, and no puncture was necessary from the 10th day after the start of LTRA. Interferon α (IFN-α) was administered from the 15th day after the start of LTRA. Thereafter, his anemia and thrombocytopenia gradually improved, the ascites disappeared, the mast cells in his bone marrow were significantly reduced, and the Asp816Val mutation disappeared. Because persistent monocytosis was evident, he was suspected of chronic myelomonocytic leukemia but has not been diagnosed and is undergoing watchful waiting. This was considered to be a rare case of refractory ascites in which IFN-α was effective and LTRA might have been beneficial.
Asunto(s)
Ascitis/etiología , Interferón-alfa/uso terapéutico , Antagonistas de Leucotrieno/uso terapéutico , Mastocitosis Sistémica , Anciano , Humanos , Masculino , Mastocitos , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/tratamiento farmacológicoRESUMEN
Although induction immunochemotherapy including high-dose cytarabine and rituximab followed by high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) is recommended for younger patients (≤65 years old) with untreated mantle cell lymphoma (MCL), no standard induction and HDC regimen has been established. We conducted a phase II study of induction immunochemotherapy of R-High-CHOP/CHASER followed by HDC of LEED with ASCT in younger patients with untreated advanced MCL. Eligibility criteria included untreated MCL, stage II bulky to IV, and age 20-65 years. Patients received 1 cycle of R-High-CHOP followed by 3 cycles of CHASER every 3 weeks. Peripheral blood stem cells (PBSC) were harvested during CHASER. LEED with ASCT was delivered to patients who responded to R-High-CHOP/CHASER. Primary endpoint was 2-year progression-free survival (PFS). From June 2008 to June 2012, 45 patients (median age 59 years; range 38-65 years) were enrolled. PBSC were successfully harvested from 36 of 43 patients. Thirty-five patients completed ASCT. Two-year PFS was 77% (80% CI 68-84), which met the primary endpoint. Five-year PFS and overall survival were 52% (95% CI 34-68%) and 71% (95% CI 51-84%), respectively. Overall response and complete response rates after induction immunochemotherapy were 96% and 82%, respectively. The most common grade 4 toxicities were hematological. In younger patients with untreated MCL, R-High-CHOP/CHASER/LEED with ASCT showed high efficacy and acceptable toxicity, and it can now be considered a standard treatment option.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto/terapia , Melfalán/uso terapéutico , Rituximab/uso terapéutico , Adulto , Anciano , Antígenos de Neoplasias/análisis , Terapia Combinada , Ciclofosfamida/uso terapéutico , Citarabina/uso terapéutico , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Humanos , Inmunoterapia/métodos , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Trasplante Autólogo , Vincristina/uso terapéutico , Adulto JovenRESUMEN
The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 32-79 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4-89.4%] and 61.0% (95%CI: 44.5-75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95%CI: 36.4-67.5%) and 73.2% (95%CI: 56.8-84.1%), respectively. The younger patients (≤ 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade ≥ 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células T Periférico/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/toxicidad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/toxicidad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Etopósido/toxicidad , Neutropenia Febril/inducido químicamente , Humanos , Linfoma de Células T Periférico/complicaciones , Persona de Mediana Edad , Neutropenia/inducido químicamente , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Prednisona/toxicidad , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/toxicidadRESUMEN
Epstein-Barr virus (EBV)-DNA was prospectively analyzed in plasma and mononuclear cells (MNCs) from peripheral blood in patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, to evaluate the clinical significance for diagnosis, monitoring the tumor burden, and prognostication. Thirty-three patients were enrolled, and 32 were evaluable. Pretreatment plasma and MNC EBV-DNA was detectable in 14 (range, 50-71 000 copies/mL) and 6 patients (range, 20-780 copies/µg DNA), respectively, and both were well correlated (r = 0.8741, P < .0001). Detectable plasma EBV-DNA was associated with higher clinical stage (P = .02), presence of B symptoms (P = .02), worse performance status (P = .02), and higher serum soluble IL-2 receptor level (P < .0001). Twenty-two patients attained complete response. Plasma EBV-DNA level was significantly higher in nonresponders than in responders (mean, 16,472 vs 2,645 copies/mL; P = .02). Multivariate analysis showed clinical stage (hazard ratio, 9.0; 95% confidence interval, 1.8%-45.0%) and pretreatment plasma EBV-DNA (hazard ratio, 10.6; 95% confidence interval, 1.3%-87.0%) were significant prognostic factors. Three-year overall survival of plasma EBV-DNA positive and negative patients was 42.9% and 94.4%, respectively (P = .0009). Plasma was a preferable sample for this purpose in NK/T-cell lymphoma, nasal type, and EBV-DNA level was a good indicator for response and overall survival.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4/genética , Linfoma Extranodal de Células NK-T , Neoplasias Nasales/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral/sangre , ADN Viral/metabolismo , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/virología , Femenino , Dosificación de Gen/genética , Humanos , Leucocitos Mononucleares/virología , Linfoma Extranodal de Células NK-T/inmunología , Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/virología , Masculino , Persona de Mediana Edad , Neoplasias Nasales/inmunología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Adulto JovenRESUMEN
Multiple myeloma (MM) is still extremely difficult to cure, and new therapeutic drugs are needed. We recently found that integrin ß7 is constitutively activated in MM cells, and chimeric antigen receptor (CAR) T cells targeting activated integrin ß7 have a significant anti-MM effect. In this study, we performed flow cytometry analysis of the expression of activated integrin ß7 in bone marrow cells from 137 symptomatic MM patients. In 60/137 (44%) MM patients, activated integrin ß7 was detected in most MM cells (> 80% of MM cells were in the positive gate). Activated integrin ß7 was highly expressed in MM cells even in heavily treated patients. It also showed high expression in many CD38lo/-CD138-CD19+B cells, which reportedly include clonotypic B cells, in the bone marrow of MM patients. Taken together, these results suggest that CAR T-cell therapy targeting activated integrin ß7 has the potential to benefit many patients with relapsed or refractory MM.
Asunto(s)
Cadenas beta de Integrinas/análisis , Mieloma Múltiple/patología , Anciano , Células de la Médula Ósea/patología , Femenino , Citometría de Flujo , Humanos , Inmunoterapia Adoptiva , Masculino , Mieloma Múltiple/terapia , Células Plasmáticas/patologíaRESUMEN
An 80-year-old man presented with the accumulation of pleural fluid in the right thoracic cavity. Serum electrophoresis revealed an M-component and immunofixation confirmed IgM/λ. The level of IgM was 1,526 mg/dL. Imaging studies showed an infiltrative condition of the ipsilateral lung parenchyma. The fluid contained abundant neoplastic cells with the morphological and immunophenotypic features of plasma cells, which expressed IgM/λ monoclonal immunoglobulins on the cell surface and in the cytoplasm. The karyotype was 48,XY,+3,add(9)(p13),+12,add(14)(q32),del(16)(q22),-18,+mar, and a series of fluorescence in situ hybridization studies demonstrated that the add(14) chromosome represented der(14)t(14;18)(q32;q21), at which the MALT1-immunoglobulin heavy-chain (IGH) fusion gene was localized. A long-distance polymerase chain reaction amplified the fragment encompassing the two genes, showing that the junction occurred at the J6 segment of IGH and 3.7-kb upstream of the MALT1 breakpoint cluster. We propose that this case represents an extreme form of the plasmacytic differentiation of extranodal marginal zone lymphoma that developed in the lung.
Asunto(s)
Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Cadenas Pesadas de Inmunoglobulina , Neoplasias Pulmonares , Linfoma de Células B de la Zona Marginal , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Proteínas de Fusión Oncogénica , Células Plasmáticas , Cavidad Pleural , Translocación Genética , Macroglobulinemia de Waldenström , Anciano de 80 o más Años , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 14/metabolismo , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 18/metabolismo , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/patología , Masculino , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas/genética , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , Cavidad Pleural/metabolismo , Cavidad Pleural/patología , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/metabolismo , Macroglobulinemia de Waldenström/patologíaRESUMEN
Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), and it has been suggested that lymphocyte recovery affects survival after HSCT. However, few studies have examined lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease. We retrospectively evaluated early lymphocyte recovery after HSCT among Japanese adults who received MMF prophylaxis. Patients were divided into two groups according to their median absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the "low ALC group" (≤ 0.22 × 109 cells/L) and the "high ALC group" (> 0.22 × 109 cells/L). With a median follow-up of 317 days, the high ALC group showed significantly better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02). The high ALC group also tended to have better non-relapse mortality than the low ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P = 0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC on day 28 after HSCT was effective in predicting overall survival and non-relapse mortality.
Asunto(s)
Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Recuento de Linfocitos , Ácido Micofenólico/administración & dosificación , Adulto , Anciano , Aloinjertos , Pueblo Asiatico , Femenino , Estudios de Seguimiento , Predicción , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR). Of the 68 eligible patients, 38.2% were women, the median age was 55.0 years, and the median duration of imatinib treatment was 97.5 months. The 12-month TFR rate was 67.6%. Patients who lost MMR were immediately treated with imatinib again; all re-achieved MMR. Three-year treatment-free survival (TFS) was estimated as 64.6% using the Kaplan-Meier method. Undetectable molecular residual disease (UMRD) was defined as no BCR-ABL1 in > 100,000 ABL1 control genes using international scale polymerase chain reaction. UMRD at the study baseline was found to be predictive of continuation of TFR. Our findings suggest that CML patients who meet all the eligibility criteria that have commonly been used in the TFR trials are able to discontinue imatinib use safely. TFR may thus be valuable as a new goal for CML treatment in Japan.
Asunto(s)
Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/genética , Supervivencia sin Enfermedad , Femenino , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mieloide de Fase Crónica/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Resultado del TratamientoRESUMEN
To identify strategies for reducing emesis induced by the CHOP regimen, which includes high-dose steroids, we prospectively evaluated the efficacy of palonosetron in Japanese patients. Palonosetron was administered at a dose of 0.75 mg via intravenous injection over 30 min before chemotherapy on day 1. Patients kept diaries of chemotherapy-induced nausea and vomiting (CINV) incidence from the start of chemotherapy until 168 h afterwards, in which they documented the occurrence and severity of nausea, vomiting, anorexia, and the use of rescue medication. The primary endpoint was the overall occurrence rate of nausea, vomiting, and anorexia; these rates were 56, 12, and 62 %, respectively, including all grades. The rates and severity of symptoms tended to worsen 120-168 h after completing oral prednisolone. We defined complete response (CR) as no vomiting and no use of rescue therapy. The CR rates of post palonosetron 0.75 mg treatment in the acute (0-24 h), delayed (24-168 h), and overall phases (0-168 h) were 86, 66, and 62 %, respectively. Antiemetic strategies of CHOP regimen for day 6 and, thereafter, should be investigated.
Asunto(s)
Antieméticos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Isoquinolinas/uso terapéutico , Linfoma/tratamiento farmacológico , Náusea/tratamiento farmacológico , Quinuclidinas/uso terapéutico , Antagonistas de la Serotonina/uso terapéutico , Vómitos/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Japón/epidemiología , Linfoma/epidemiología , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Palonosetrón , Prednisolona/efectos adversos , Prednisolona/uso terapéutico , Estudios Prospectivos , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vómitos/inducido químicamente , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: Flow cytometric immunophenotypic analysis (FC) and cytogenetic analysis are essential techniques for the diagnosis and classification of many hematologic disorders. The roles of these analyses in B-cell lymphoma to detect bone marrow (BM) involvement in clinical staging and to evaluate the effectiveness of treatments have not yet been determined. The aim of this study was to evaluate the usefulness of FC and cytogenetic analysis in the assessment of BM involvement in B-cell lymphoma. DESIGN AND METHODS: We retrospectively analyzed the usefulness of three-color FC and cytogenetic analysis in detecting BM involvement by examining 104 BM specimens from patients with B-cell lymphoma. RESULTS: By morphologic evaluation of BM biopsy (BMB), the BM was involved in 11 specimens (10.6%), not involved in 92 specimens (88.5%) and involvement could not be determined in 1 specimen (0.9%). FC identified a monoclonal B-cell population in 24 samples (23.1%). FC detected BM involvement in all but one BMB positive sample, and showed negative results in a BMB undetermined sample. Conclusively, FC found a monoclonal B-cell population in 14 of 92 BMB negative samples (15.2%). In particular, FC detected smaller amounts of BM involvement than did morphologic evaluation. Cytogenetic analysis revealed clonal abnormalities in only 9 of 104 samples (8.7%). However, 2 of these 9 samples were from patients with aggressive lymphoma with complex structural chromosomal abnormalities detectable only by cytogenetic analysis. INTERPRETATION AND CONCLUSIONS: Although morphologic evaluation of adequate amounts of BMB specimens remains essential for the evaluation of BM involvement, three-color FC is more sensitive in detecting BM disease than morphologic or cytogenetic analysis. Cytogenetic analysis seems to have low sensitivity and specificity, but this method may improve the detection of BM involvement in a small number of aggressive lymphomas that have many mitotic cells.
Asunto(s)
Examen de la Médula Ósea/métodos , Médula Ósea/patología , Reordenamiento Génico de Cadena Pesada de Linfocito B , Cariotipificación , Linfoma de Células B/patología , Linfocitos B/patología , Biopsia , Tamaño de la Célula , Aberraciones Cromosómicas , Células Clonales/patología , Femenino , Citometría de Flujo/métodos , Humanos , Ilion/patología , Técnicas para Inmunoenzimas , Inmunofenotipificación , Linfoma de Células B/clasificación , Linfoma de Células B/genética , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
Follicular lymphoma is characterized genetically by t(14;18)(q32;q21), whereas t(18;22)(q21;q11), a rare variant form of t(14;18), has been preferentially observed in chronic lymphocytic leukemia (CLL). We describe here an unusual case of follicular lymphoma with a t(18;22)(q21;q11), that progressed to diffuse large cell lymphoma with a novel t(2;6)(p12;q23). Spectral karyotyping revealed that add(2)(p12) and add(6)(q23) were derived from a t(2;6)(p12;q23). Fluorescence in situ hybridization analysis confirmed rearrangements of the BCL2 gene at 18q21 and the BCL6 gene at 3q27. Our results indicate that a reciprocal translocation involving 6q23 could be implicated in the progression of follicular lymphoma and that t(18;22) may have a specific role in the pathogenesis of follicular lymphoma as well as CLL.
Asunto(s)
Linfoma Folicular/genética , Linfoma de Células B Grandes Difuso/genética , Translocación Genética , Adulto , Transformación Celular Neoplásica/genética , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 6 , Análisis Citogenético , Progresión de la Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana EdadRESUMEN
Cytogenetic abnormalities are observed in approximately one half of cases of myelodysplastic syndrome (MDS). Partial or complete chromosome losses and chromosome gains are frequently found, but there is a relatively high incidence of unbalanced translocations in MDS. We describe here two cases of MDS with an unbalanced translocation, der(11)t(11;12)(q23;q13). Both patients were 69 years of age and diagnosed with refractory anemia with excess of blasts in transformation (RAEB-t) according to the high percentage of blasts in the peripheral blood. Cytoplasmic hypogranulation of neutrophils was evident as a dysplastic change. The blasts were positive for CD4 and CD41a as well as CD13, CD33, CD34 and HLA-DR in both cases. Chromosome analysis showed complex karyotypes including a der(11)t(1;11)(q11;p15)t(11;12)(q23;q13) in case 1 and der(11)t(11;12)(q23;q13) in case 2 plus several marker chromosomes. Spectral karyotyping confirmed the der(11)t(11; 12)(q23;q13) and clarified the origin of marker chromosomes, resulting in del(5q) and del(7q). Fluorescence in situ hybridization (FISH) analyses with a probe for the MLL gene demonstrated that the breakpoints at 11q23 were telomeric to the MLL gene in both cases. FISH also showed that the breakpoint at 11p15 of the case 1 was telomeric to the NUP98 gene. Considering another reported case, our results indicate that the der(11)t(11;12)(q23;q13) is a recurrent cytogenetic abnormality and may be involved in the pathogenesis of advanced-stage MDS.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 11 , Síndromes Mielodisplásicos/genética , Translocación Genética , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , MasculinoRESUMEN
A rheumatoid arthritis (RA) patient treated with low-dose methotrexate (MTX) therapy suffered from hemophagocytic syndrome (HPS) associated with B-cell lymphoma (B-LAHS). Administration of acyclovir and intravenous immunoglobulin promptly resolved laboratory test abnormalities accompanied with HPS. Moreover, hemophagocytic histiocytes and lymphoma cells in the bone marrow disappeared without anti-cancer therapy. Two months after reintroduction of MTX for RA flare, lymphoma re-grew rapidly without bone marrow involvement and HPS. Two cycles of combination chemotherapy induced the lymphoma to a complete remission/unconfirmed (CRu), but then the chemotherapy was discontinued due to severe side effects. In this case, on the basis of RA and MTX induced immunosuppressive state, Epstein-Barr virus (EBV) infection was associated with the development of HPS and lymphoma. Anti-viral therapy alone was effective against HPS and lymphoma at initial presentation and improved her general condition. This case indicates that anti-cancer therapy should be preceded by anti-viral therapy and withdrawal of immunosuppressive therapy in patients under immunosuppressive therapy, as long as the clinical situation permits.
Asunto(s)
Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Histiocitosis de Células no Langerhans/tratamiento farmacológico , Linfoma de Células B/tratamiento farmacológico , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Histiocitosis de Células no Langerhans/etiología , Humanos , Linfoma de Células B/complicaciones , Metotrexato/uso terapéutico , SíndromeRESUMEN
A 50-year-old man developed invasive pulmonary aspergillosis after induction chemotherapy for acute lymphoblastic leukemia. He was treated with 5-fluorocytosine and intravenous amphotericin B (AMPH-B). During antifungal therapy, he developed aspergillus pericarditis and complete atrioventricular (A-V) block. The pericardial effusion was decreased and the A-V block was improved after treatment with intravenous and intrapericardial instillation of AMPH-B. Because the patient's renal function deteriorated, AMPH-B was replaced with itraconazol after the latex agglutination (LA) test for an aspergillus-specific antigen showed a negative result. The patient, however, died from disseminated aspergillosis. Aspergillus DNA was detected in retrospective analysis of the serum which had been negative with the LA test. This case indicates that LA is not sufficient for diagnosis and post therapy evaluation of invasive aspergillosis. PCR or other methods should be used concomitantly with LA. Intrapericardial instillation of AMPH-B might be effective for patients with aspergillus pericarditis in whom surgical treatment is not indicated.
Asunto(s)
Aspergilosis/etiología , Bloqueo Cardíaco/etiología , Enfermedades Pulmonares Fúngicas/etiología , Pericarditis/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Insuficiencia de la Válvula Aórtica/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL. PATIENTS AND METHODS: Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years. RESULTS: A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 10(9)/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non-high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated. CONCLUSION: In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study.
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Antineoplásicos/efectos adversos , Arsenicales/efectos adversos , Electrocardiografía/efectos de los fármacos , Óxidos/efectos adversos , Trióxido de Arsénico , Femenino , Humanos , MasculinoRESUMEN
Among B-cell non-Hodgkin's lymphomas, neural cell adhesion molecule/CD56 expression is exceptional. In this study, seven cases of CD56-positive diffuse large B-cell lymphoma (DLBCL) are described. The frequency of CD56-positive DLBCL was 7% in our hospital. Four of seven (57.1%) cases expressed both CD10 and bcl-6 suggestive of a germinal center B-cell phenotype. Six of seven (85.7%) cases expressed bcl-6. Two cases expressed aberrant T cell-associated antigens, one each of CD7 and CD8. However, none of these seven cases showed CD5 expression. No significant difference was observed between CD56-positive and CD56-negative DLBCL in terms of the five international prognostic index risk factors. However, all seven cases had at least one extranodal involvement and showed a good response to initial treatment. The predominance of extranodal involvement in our series may be associated with the adhesion-related function of CD56. A high frequency of bcl-6 expression may be associated with a more favorable clinical course and prognosis.
Asunto(s)
Antígeno CD56/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Linfoma de Células B Grandes Difuso/metabolismo , Adulto , Antígeno CD56/inmunología , Citometría de Flujo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-6 , Estudios Retrospectivos , Adulto JovenRESUMEN
This report concerns a rare case of follicular lymphoma with features suggestive of primary hepatic lymphoma. At the disease onset, multiple nodular lesions in the liver and small para-aortic nodes were detected by abdominal magnetic resonance imaging without generalized lymphadenopathy. After careful observation for three months, lymphadenopathy was observed in the right occipital, para-aortic, and bilateral inguinal regions. The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and achieved complete remission for more than 2 years. To the best of our knowledge, this is the ninth report of primary hepatic follicular lymphoma. Insufficient cases have been reported to determine the long-term outcome and clinical characteristics of primary hepatic follicular lymphoma. However, it seems that patients with primary hepatic follicular lymphoma that are treated with appropriate chemotherapy with or without surgical resection have favorable outcomes.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Colecistitis/patología , Ciclofosfamida , Doxorrubicina , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/fisiopatología , Linfoma Folicular/fisiopatología , Imagen por Resonancia Magnética , Prednisona , Inducción de Remisión , Rituximab , VincristinaRESUMEN
A 67-year-old woman presented with a pleural effusion and a tumor in the right pleural wall. Histological examination of thoracoscopic tumor and pleural biopsy specimens showed infiltration by medium sized cells, some of which showed plasmacytoid differentiation. In view of the presence of IgM paraproteinemia and bone marrow involvement by lymphoma cells, the patient was diagnosed tentatively as having lymphoplasmacytic lymphoma (LPL). However, chromosomal analysis of the cells in the pleural fluid detected t(14;18)(q32;q21), while fluorescence in situ hybridization was positive for 11% of the MALT1 split signal. Because of the presence of characteristic genetic abnormalities and notable extranodal involvement, the patient was diagnosed as having MALT lymphoma. She was treated with three courses of cladribine and rituximab, and achieved complete regression of the tumor. In this case the detection of t(14;18)(q32;q21) involving IGH and MALT1 was useful for the differential diagnosis of LPL and MALT lymphoma.